Glycoproteins are important constituents of the cell surface of all mammalian cells, both normal and abnormal, many of which serve as antigens in autologous, syngeneic and xenogeneic immunizations. They have been implicated in many other properties of cells which involve specific recognition and interactions. The main objective of this study is to analyze the surface glycoproteins of cultured cells from malignant melanoma and other human tumors. One aspect which will be studied is the apparent high degree of sialylation exhibited by the cell surface glycoproteins of melanoma. This is in contrast to other tumors and normal cells studied and may be related to the biological characteristics of melanoma. The remainder of the study will emphasize two antigens of melanoma and other tumors: Gp110 and DR or Ia-like antigens. The former, which is detected by a specific rabbit antiserum, appears to be the major glycoprotein of a number of cell types, both normal and malignant. Its significance lies in the possibility that it may inhibit structural differences in its carbohydrate chains in malignant as compared to normal cells. Ia antigens were originally considered to be confined to cells of the hematopoietic system but have recently been found to occur on other cells including melanoma. Several aspects of the expression of Ia in tumors will be studied: (1) quantitation of Ia antigen in different melanoma lines, in melanoma tumors and in other tissues and cells, both normal and abnormal; (2) structural characteristics of melanoma Ia antigen and (3) comparison of melanoma Ia with lymphocyte Ia using cells derived from the same individual. The significance of Ia expression in melanoma lies in its possible role as a differentiation antigen and in influencing the immune response to the tumor.